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Supplementary Figure 4 from Computational Algorithm-Driven Evaluation of Monocytic Myeloid-Derived Suppressor Cell Frequency for Prediction of Clinical Outcomes

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posted on 2023-04-03, 23:10 authored by Shigehisa Kitano, Michael A. Postow, Carly G.K. Ziegler, Deborah Kuk, Katherine S. Panageas, Czrina Cortez, Teresa Rasalan, Mathew Adamow, Jianda Yuan, Philip Wong, Gregoire Altan-Bonnet, Jedd D. Wolchok, Alexander M. Lesokhin

PDF file - 101K, Supplemental Figure 4. Different summary statistics can be applied to measure HLA-DR expression on lineage negative, CD14+CD11b+ cells and assess relationship to overall survival (using maximum logrank statistics as described in Methods). CV was used as a self-normalizing measurement that was preferred to eliminate non-biological variation in clinical measurements (e.g. day-to-day variation, differences in sample handling and FACS acquisition).

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ARTICLE ABSTRACT

Evaluation of myeloid-derived suppressor cells (MDSC), a cell type implicated in T-cell suppression, may inform immune status. However, a uniform methodology is necessary for prospective testing as a biomarker. We report the use of a computational algorithm-driven analysis of whole blood and cryopreserved samples for monocytic MDSC (m-MDSC) quantity that removes variables related to blood processing and user definitions. Applying these methods to samples from patients with melanoma identifies differing frequency distribution of m-MDSC relative to that in healthy donors. Patients with a pretreatment m-MDSC frequency outside a preliminary definition of healthy donor range (<14.9%) were significantly more likely to achieve prolonged overall survival following treatment with ipilimumab, an antibody that promotes T-cell activation and proliferation. m-MDSC frequencies were inversely correlated with peripheral CD8+ T-cell expansion following ipilimumab. Algorithm-driven analysis may enable not only development of a novel pretreatment biomarker for ipilimumab therapy, but also prospective validation of peripheral blood m-MDSCs as a biomarker in multiple disease settings. Cancer Immunol Res; 2(8); 812–21. ©2014 AACR.

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